Index and Non-index Pain Endpoints in Radiation Therapy for Painful Tumors: A Secondary Analysis of a Prospective Observational Study

Abstract

Improving pain interference in daily activities, rather than mere pain reduction, is a desirable endpoint for palliative radiation therapy. The association between pain response and pain interference has been studied almost exclusively in patients with painful bone metastases (PBMs), whereas non-index pain has hardly been explored in palliative radiation therapy. We investigated whether index and non-index pain endpoints are associated with changes in pain interference in patients with PBMs and in those with painful non-bone-metastasis tumors (PNTs). Brief Pain Inventory data collected at baseline and at 2 months post-treatment were used to calculate differences in pain interference scores. The treating radiation oncologists differentiated between index pain caused by the irradiated tumor and ‘non-index pain’, the cause of which was not irradiated. Pain response in terms of the index pain was assessed using the International Consensus Endpoint for bone metastases. Patients were diagnosed with predominance of other pain (POP) if non-index pain of malignant or unknown origin was present and had a greater pain score than the index pain. Of 302 patients, 127 (42%) had PBMs and 175 (58%) had PNTs. The median pain interference score, which is based on the mean of the 7 subscale items, decreased to a greater extent among responders than among nonresponders (PBM group: -3.43 vs. -0.57 [P = .005]; PNT group: -2.43 vs. -0.29 [P < .001]). Moreover, patients without POP experienced a greater reduction in their median pain interference score than did those with POP (PBM group: -2.71 vs. -0.43 [P = .004]; PNT group: -2.00 vs. +1.57 [P = .007]). Jonckheere-Terpstra test showed a significant trend across four pain response categories in patients with PBMs and those with PNTs (P < .001 for both). The index and non-index pain endpoints were positively and negatively associated with improvement in pain interference, respectively. There was no apparent difference between patients with PBMs and PNTs in terms of the associations of these endpoints with pain interference. In the next update of the international consensus on palliative radiation therapy endpoints, it may be worth exploring whether non-index pain endpoints should be utilized in radiation therapy for PBMs and whether the International Consensus Endpoint can be used to assess pain palliation in patients with PNTs.